Practice Essentials

Type 1 complex regional pain syndrome (CRPS 1), formerly known as reflex sympathetic dystrophy (RSD), is a clinical syndrome of variable course and unknown cause characterized by pain, swelling, and vasomotor dysfunction of an extremity. This condition is often the result of trauma or surgery. Limb immobility may lead to CRPS 1; in a hemiplegic upper limb after stroke, the syndrome is often termed shoulder-hand syndrome. CRPS 1 may also develop in the absence of an identifiable precipitating event.

Current taxonomy categorizes CRPS 1 as occurring in the absence of definable nerve injury.
[1] Type 2 CRPS, causalgia, develops after nerve injury; the term causalgia was coined by Mitchell in 1864 and derives from the Greek for burning pain. In patients with either type 1 or type 2 CRPS, sympathetic mediation of the pain (ie, improvement with sympathetic blockade) may or may not be evident.

CRPS 1 is largely a clinical diagnosis (see Presentation and DDx). Two major approaches to the treatment of early CRPS 1 are sympathetic blockade and anti-inflammatory therapy. Surgical sympathectomy may be considered in patients with refractory CRPS 1 that had initially responded to sympathetic blockade. Spinal cord stimulation is another surgical option. (See Treatment and Medication.)

Pathophysiology

The pathogenesis of CRPS 1 is unknown. Three conditions are deemed important in the development of CRPS 1, as follows:

A persistent painful lesion

A predisposition or susceptibility to developing the syndrome

An abnormal sympathetic reflex

Susceptibility factors are unknown and may include genetic predisposition (HLA typing)
[2, 3, 4] and, in some patients, a tendency toward increased sympathetic activity. This includes cold hands, hyperhidrosis, or a history of fainting.

Healthy individuals have a sympathetic response to injury, with vasoconstriction designed to prevent blood loss and swelling. This initial response soon subsides and gives way to vasodilatation and increased capillary permeability, allowing tissue repair.

In patients with CRPS 1, this sympathetic response continues unabated. The reasons for the perpetuation of the response are unknown but may be related to central dysregulation of nociceptive impulses. This dysregulation may be mediated by wide dynamic range neurons in the spinal cord.

Prolonged ischemia caused by the vasoconstriction produces more pain, establishing a reflex arc that promotes further sympathetic discharge and vasospasm. This is compounded by the local response to trauma, with liberation of substantial amounts of proinflammatory mediators, such as histamine, serotonin, and bradykinin.

The result is a swollen, painful, stiff, nonfunctioning extremity. At least partial sympathetic mediation of this phenomenon is likely because of the ability of sympathetic nerve blockade to relieve pain and other features of CRPS 1 in some patients.

Numerous studies have reported altered brain function in CRPS 1. Researchers have also documented structural alterations in the brain. Pleger et al reported that magnetic resonance imaging (MRI) in patients with CRPS 1 showed altered gray matter structure in dorsomedial prefrontal cortex, as well as increases in gray matter density in the motor cortex contralateral to the affected limb, which were inversely related to decreased white matter density of the internal capsule within that brain hemisphere.
[5]

A study by Barad that used structural MRI found that compared with controls, patients with complex regional pain syndrome had decreased gray matter volume in several pain-affect regions (including the dorsal insula, left orbitofrontal cortex, and several aspects of the cingulate cortex) and increased gray matter volume in the bilateral dorsal putamen and right hypothalamus.
[6]

Lee et al found that the right dorsolateral prefrontal cortex and left ventromedial prefrontal cortex were significantly thinner in patients with CRPS than in healthy controls. In addition, CRPS patients had longer stop-signal task reaction times and made more perseveration errors on the Wisconsin Card Sorting Test.
[7]

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Etiology

CRPS 1 is usually posttraumatic or postsurgical; however, it can occur in a previously healthy extremity with no known trigger.

Penetrating wounds that can lead to CRPS 1 include the following:

Lacerations

Abrasions

Venipuncture

Intramuscular injection of medication or illicit drugs

Gunshot wounds

Other traumatic causes of CRPS 1 include the following:

Crush injuries and blunt trauma

Neck or shoulder injuries

Acute traumatic carpal tunnel syndrome

Chest trauma

Sprain, fracture, or dislocation

Postsurgery CRPS 1 has been reported after the following procedures:

Carpal tunnel release

Dental extractions

Cervical rib resection

Fracture repair (Colles fracture)

Arthroscopy

Local disorders associated with CRPS 1 include the following:

Nerve compression syndromes

Arthritis

Tissue ischemia

Stenosing tenosynovitis

Systemic disorders associated with CRPS 1 include the following:

Myocardial infarction

Stroke

Pancoast tumor

Pancreatic cancer

Herpes zoster

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Epidemiology

Frequency

In the United States, an estimated 5% of patients who experience trauma to the upper extremity develop CRPS 1, although this figure is not known with certainty because of confusion over the diagnosis. Extremity immobilization can trigger CRPS 1. Without prophylactic measures (active physical therapy), CRPS 1 can develop in 12-20% of people who experience a hemiplegic stroke.

Race-, Sex-, and Age-related Demographics

No racial predilection exists for CRPS 1. Sexual distribution is equal. Although CRPS 1 can occur in children, the age of onset in most patients CRPS 1 is 30-60 years, and the mean age is 49 years.
[8]

A Scottish study estimated that the incidence of CRPS in children 5-15 years of age is 1.2 per 100,000. Girls constituted 73% of patients. Most cases involed a single site, with legs often affected than arms and the right side more often affected than the left. Clear trauma had occurred at the onset of the illness in most cases. Diagnosis was made a median of 2 months (range, 1-12) after the onset of symptoms.
[9]

[Guideline] National Institute for Health and Care Excellence. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin. NICE. Available at http://www.nice.org.uk/guidance/ta159. Accessed: September 26, 2014.

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital